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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #78495
Title: INTEGRIN MAC-1 AND BETA-AMYLOID IN MICROGLIAL RELEASE OF NITRIC OXIDE

Author
item GOODWIN, JEFFREY - IA STATE UNIV., AMES, IA
item Kehrli Jr, Marcus
item UEMURA, ETSURO - IA STATE UNIV., AMES, IA

Submitted to: Brain Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Alzheimer's disease (AD) is a degenerative disorder of the nervous system characterized clinically by loss of memory and other cognitive functions and pathologically by a development of plaques in selected tissues of the brain. Amyloid protein (AP) is the major extracellular protein constituent of AD plaques. The cellular source and pathological effects of AP deposits sin the AD patient's brain is controversial. One of the cell types in the brain that AP affects is the microglial cell. Research reported here identifies a role for the beta-2 integrins in triggering production of nitric oxide by microglial cells when stimulated with forms of AP. Nitric oxide production in AD brains may contribute to AD plaque build-up and progression of Alzheimer's disease. The main benefit of this work is the expansion of basic immunology knowledge that can now be exploited in the study of this neurodegenerative disease.

Technical Abstract: The beta-amyloid protein associated with Alzheimer's Disease (AD) has been well characterized biochemically; however, its primary biological function and mode of action in AD has not been determined. We have shown previously that beta-amyloid (beta25-35), in combination with interferon gamma (IFN-gamma), can induce nitric oxide release from cultured hippocampal microglial cells. In the present study, binding of beta-amyloid with the leukocyte integrin Mac-1, a cell surface receptor on microglia, was studied by observing: (1) inhibition of beta-amyloid (beta25-35)-mediated release of nitric oxide from cultured microglial cells following exposure to monoclonal antibodies against Mac-1 (anti-CD18 and anti-CD11b); and (2) competitive binding of fluorochrome-labeled beta25-35 with anti-CD18 or anti-CD11b using fluorescent flow cytometry. Wt.3 (anti-CD18 antibody) and OX42 (anti-CD11b antibody) were as effective as opsonized zymosan at inducing the release of nitric oxide from microglia. Furthermore, Wt.3 and OX42 acted synergistically to induce maximum nitric oxide release. An interaction between beta-amyloid and CD18 of Mac-1 was evidenced by the suppressive action of beta25-35 on Wt.3-mediated release of nitric oxide and the synergistic action between OX42 and beta25-35 in inducing nitric oxide release from microglia.